In a patient with Crohn's disease and fistulizing disease who has developed antibodies against Infliximab (infliximab), what is the next drug to consider?

Next Drug Choice for Fistulizing Crohn's Disease After Infliximab Antibody Development

For patients with Crohn's disease and fistulizing disease who have developed antibodies against infliximab, adalimumab or ustekinumab should be used as the next treatment option.

Treatment Algorithm for Anti-Infliximab Antibody Patients

First-Line Options After Infliximab Failure

1. Adalimumab

   • Recommended by the AGA for patients with secondary non-response to infliximab 1
   • Demonstrated efficacy in patients who lost response to infliximab 2
   • 41% of patients with fistulizing disease experienced fistula improvement at week 4 2

2. Ustekinumab

   • Strongly recommended by the AGA for patients with secondary non-response to infliximab 1
   • Demonstrated effectiveness for fistula remission (RR, 0.85; 95% CI, 0.73-1.99) 1
   • Recommended over certolizumab pegol for induction of remission 1

Second-Line Option

• Vedolizumab
  • Suggested by the AGA for patients with secondary non-response to infliximab 1
  • May be effective for fistula closure (RR, 0.81; 95% CI, 0.63-1.04) 1
  • Lower certainty of evidence compared to adalimumab and ustekinumab

Evidence Quality and Considerations

The AGA Clinical Guidelines Committee provides strong recommendations for adalimumab and ustekinumab in patients who previously responded to infliximab but developed secondary non-response 1. This directly applies to patients who developed antibodies against infliximab, as antibody formation is a common mechanism of secondary non-response.

Adalimumab has specific evidence supporting its use in patients who lost response to infliximab, with 83% achieving clinical response and 41% experiencing fistula improvement at week 4 2. This makes it particularly relevant for patients with fistulizing disease.

Ustekinumab has demonstrated effectiveness specifically for fistula remission in pooled analyses, though with lower certainty evidence than infliximab 1.

Important Clinical Considerations

• Combination therapy: Consider combining the chosen biologic with antibiotics for perianal fistulas, as this is strongly recommended over biologic therapy alone 1

• Avoid certolizumab pegol: Evidence suggests it may not be effective for induction of fistula remission 1

• Monitoring: Regardless of which agent is chosen, continue regular monitoring for:

  • Clinical response (8-12 weeks after initiation)
  • Fistula drainage
  • Normalization of stool frequency
  • Ability to taper corticosteroids
  • Endoscopic healing

Pitfalls to Avoid

1. Continuing infliximab at higher doses: When antibodies to infliximab are present, simply increasing the dose is unlikely to overcome the immunogenicity.

2. Using certolizumab pegol: Despite being another anti-TNF agent, evidence suggests it may not be effective for fistula remission 1.

3. Delaying treatment switch: Prompt transition to an alternative therapy is essential to prevent disease progression and complications from active fistulizing disease.

4. Neglecting surgical evaluation: Medical therapy alone may be insufficient for complex fistulas, and surgical consultation should be considered alongside medical management.